The alterations of N-Methyl-D-aspartate receptor expressions and oxidative DNA damage in the CA1 area at the early time after ischemia-reperfusion insult

Delayed neuronal death in the CA1 of the hippocampus following global ischemia has been evoked by both the activation of N-methyl-D-aspartate receptor (NR) and the generate reactive oxygen species in the neurons. In the present study, we investigated whether oxidative DNA damages may be correlated with NR subunits (NR1 and NR2A/B) expression following ischemia insults in vivo. Thirty minutes after ischemia-reperfusion, the intensities of both NR and 8-hydroxy-2'-deoxyguanosine (8-OHdG) immunoreactivities were markedly increased in neurons of CA1. However, NR2A/B and 8-OHdG immunoreactivities were enhanced in CA1 over 24 h after ischemia although NR1 immunoreactivity was decreased. These results suggest that oxidative stress and excitotoxicity in the CA1 may simultaneously trigger neuronal damages at early time after ischemia, and free radical damage including oxidative DNA damage may eventually promote the delayed neuronal death in this region.     

Dynamics of Serum Retinol and Alpha-Tocopherol Levels According to Non-Alcoholic Fatty Liver Disease Status

The available data on the association between micronutrients in the blood and non-alcoholic fatty liver disease (NAFLD) are limited. To investigate the clinical implications of this relationship, we sought to identify the difference in the serum levels of vitamins A and E according to NAFLD status using data from the seventh Korea National Health and Nutrition Examination Survey. In this cross-sectional study of the Korean population, NAFLD and its severity were defined using prediction models. Differences in the prevalence and severity of NAFLD were analyzed according to serum retinol (vitamin A) and alpha (α)-tocopherol (vitamin E) levels. Serum levels of retinol and α-tocopherol were positively correlated with the prevalence of NAFLD. In most prediction models of the NAFLD subjects, serum retinol deficiency was significantly correlated with advanced fibrosis, while serum α-tocopherol levels did not differ between individuals with or without advanced fibrosis. Similar trends were also noted with cholesterol-adjusted levels of α-tocopherol. In summary, while circulating concentrations of retinol and α-tocopherol were positively associated with the presence of NAFLD, advanced liver fibrosis was only correlated with serum retinol levels. Our findings could provide insight into NAFLD patient care at a micronutrient level.     

Precision Tracing of Household Dengue Spread Using Inter- and Intra-Host Viral Variation Data,Kamphaeng Phet,Thailand

Dengue control approaches are best informed by granular spatial epidemiology of these viruses, yet reconstruction of inter- and intra-household transmissions is limited when analyzing case count, serologic, or genomic consensus sequence data. To determine viral spread on a finer spatial scale, we extended phylogenomic discrete trait analyses to reconstructions of house-to-house transmissions within a prospective cluster study in Kamphaeng Phet, Thailand. For additional resolution and transmission confirmation, we mapped dengue intra-host single nucleotide variants on the taxa of these time-scaled phylogenies. This approach confirmed 19 household transmissions and revealed that dengue disperses an average of 70 m per day between households in these communities. We describe an evolutionary biology framework for the resolution of dengue transmissions that cannot be differentiated based on epidemiologic and consensus genome data alone. This framework can be used as a public health tool to inform control approaches and enable precise tracing of dengue transmissions.     

Costs of Immunization Programs for 10 Vaccines in 94 Low- and Middle-Income Countries From 2011 to 2030

ObjectivesUnderstanding the level of investment needed for the 2021-2030 decade is important as the global community faces the next strategic period for vaccines and immunization programs. To assist with this goal, we estimated the aggregate costs of immunization programs for ten vaccines in 94 low- and middle-income countries from 2011 to 2030.MethodWe calculated vaccine, immunization delivery and stockpile costs for 94 low- and middle-income countries leveraging the latest available data sources. We conducted scenario analyses to vary assumptions about the relationship between delivery cost and coverage as well as vaccine prices for fully self-financing countries.ResultsThe total aggregate cost of immunization programs in 94 countries for 10 vaccines from 2011 to 2030 is $70.8 billion (confidence interval: $56.6-$93.3) under the base case scenario and $84.1 billion ($72.8-$102.7) under an incremental delivery cost scenario, with an increasing trend over two decades. The relative proportion of vaccine and delivery costs for pneumococcal conjugate, human papillomavirus, and rotavirus vaccines increase as more countries introduce these vaccines. Nine countries in accelerated transition phase bear the highest burden of the costs in the next decade, and uncertainty with vaccine prices for the 17 fully self-financing countries could lead to total costs that are 1.3-13.1 times higher than the base case scenario.ConclusionResource mobilization efforts at the global and country levels will be needed to reach the level of investment needed for the coming decade. Global-level initiatives and targeted strategies for transitioning countries will help ensure the sustainability of immunization programs.     

Systemic inflammation response index predicts all-cause mortality in patients with antineutrophil cytoplasmic antibody-associated vasculitis

International Urology and Nephrology - A systemic inflammation response index (SIRI) has been recently introduced as a tool for the assessment of the prognosis of several critical medical...     

Efficacy of testosterone replacement therapy for treating metabolic disturbances in late-onset hypogonadism: a systematic review and meta-analysis

International Urology and Nephrology - Late onset hypogonadism (LOH) is an age-dependent reduction of testosterone associated with alterations of metabolic profile, including glucose control,...     

Novel second-generation rexinoid induces growth arrest and reduces cancer cell stemness in human neuroblastoma patient-derived xenografts

IntroductionThe poor therapeutic efficacy seen with current treatments for neuroblastoma may be attributed to stem cell-like cancer cells (SCLCCs), a subpopulation of cancer cells associated with poor prognosis and disease recurrence. Retinoic acid (RA) is a differentiating agent used as maintenance therapy for high-risk neuroblastoma but nearly half of children treated with RA relapse. We hypothesized that 6-Methyl-UAB30 (6-Me), a second-generation rexinoid recently developed with a favorable toxicity profile compared to RA, would reduce cancer cell stemness in human neuroblastoma patient-derived xenografts (PDXs).MethodsCells from three neuroblastoma PDXs were treated with 6-Me and proliferation, viability, motility, and cell-cycle progression were assessed. CD133 expression, sphere formation, and mRNA abundance of stemness and differentiation markers were evaluated using flow cytometry, in vitro extreme limiting dilution analysis, and real-time PCR, respectively.ResultsTreatment with 6-Me decreased proliferation, viability, and motility, and induced cell-cycle arrest and differentiation in all three neuroblastoma PDXs. In addition, 6-Me treatment led to decreased CD133 expression, decreased sphere-forming ability, and decreased mRNA abundance of Oct4, Nanog, and Sox2, indicating decreased cancer cell stemness.Conclusions6-Me decreased oncogenicity and reduced cancer cell stemness of neuroblastoma PDXs, warranting further exploration of 6-Me as potential novel therapy for neuroblastoma.     

Clinical Significance of De Novo Malignancy After Liver Transplant: A Single-Center Study

BackgroundSeveral studies have reported that solid organ transplant recipients have a high risk for malignant tumors because the suppressed immune system fails in preventing malignant transformations. De novo malignancy after transplantation is the most common cause of death in the late period after liver transplant (LT). This study investigated the clinical significance of de novo malignancy after LT, and it is the largest study based in Korea to report long-term follow-up results associated with de novo malignancy after LT.MethodsData of 1793 adults who underwent LT in Seoul National University Hospital were retrospectively collected, and medical charts and data from the Ministry of Public Administration and Security were reviewed to examine the causes of death and de novo malignancy status. The Fisher exact test and Kaplan-Meier survival analysis were used to analyze the data.ResultsOf the 1793 recipients, 27 died of de novo malignancies. Of 875 hepatocellular carcinoma (HCC) patients, 12 died, and of 918 non-HCC patients, 15 died. De novo malignancy was the main cause of death at 5 years after LT but was not in the initial 5 years. In Korea the most common cancers that developed after LT were gastric cancer (21.4%) and lymphoma (14.3%). De novo HCC in non-HCC cases was found in 2 patients.ConclusionDe novo malignancy is a key factor affecting long-term survival after LT. Therefore, regular screening and education are important for improving long-term survival and quality of life in these patients after LT.